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Performance of Interferon-Gamma and IP-10 Release Assays for Diagnosing Latent Tuberculosis Infections in Patients with Concurrent Malaria in Tanzania

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  • Department of Pulmonary and Infectious Diseases, Nordsjaelland Hospital, Hillerød, Denmark; Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Denmark; InterACT Project, Muheza District Hospital, Muheza, Tanzania; Centre for Medical Parasitology, Department of Immunology and Microbiology and Department of Public Health, University of Copenhagen; Department of Infectious Diseases and Department of Clinical Microbiology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; National Institute for Medical Research, Tanga, Tanzania; Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark; Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark

Interferon-gamma (IFN-γ) release assays (IGRAs) are used to detect cellular immune recognition of Mycobacterium tuberculosis. The chemokine IFN-γ-inducible protein 10 (IP-10) is an alternative diagnostic biomarker to IFN-γ. Several conditions interfere with IGRA test performance. We aimed to assess the possible influence of Plasmodium falciparum infection on the IGRA test QuantiFERON-TB GOLD® In-Tube (QFT) test and an in-house IP-10 release assay. In total, 241 Tanzanian adults were included; 184 patients with uncomplicated malaria (88 human immunodeficiency virus [HIV] coinfected) and 57 HIV-infected patients without malaria infection. Malaria was treated with artemether–lumefantrine (Coartem®). QFT testing was performed before initiation of malaria treatment and at days 7 and 42. In total, 172 patients completed follow-up. IFN-γ and IP-10 was measured in QFT supernatants. We found that during malaria infection IFN-γ and IP-10 levels in the unstimulated samples were elevated, mitogen responsiveness was impaired, and CD4 cell counts were decreased. These alterations reverted after malaria treatment. Concurrent malaria infection did not affect QFT test results, whereas there were more indeterminate IP-10 results during acute malaria infection. We suggest that IGRA and IP-10 release assay results of malaria patients should be interpreted with caution and that testing preferably should be postponed until after malaria treatment.

Author Notes

* Address correspondence to Camilla H. Drabe, Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Kettegaard Alle 30, 2650 Hvidovre, Denmark. E-mail: camilla.h.drabe@gmail.com

Financial support: The ACT Consortium was funded through a grant from the Bill & Melinda Gates Foundation to the London School of Hygiene and Tropical Medicine. This sub-study was partly funded by Danida. Camilla H. Drabe is a recipient of a research grant from Copenhagen University Hospital Nordsjaelland Hospital, Hillerød.

Disclosure: PR and MR hold a pending patent on the IP-10 release assay. MR is employed at Statens Serum Institut who holds and licenses IP on immunodiagnostic antigens included in QuantiFERON®. No other conflicts of interests declared.

Authors' addresses: Camilla H. Drabe, Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Kettegaard Alle 30, 2650 Hvidovre, Denmark, E-mail: camilla.h.drabe@gmail.com. Lasse S. Vestergaard, InterACT Project, Muheza District Hospital, Muheza, Tanzania, Department of Immunology and Microbiology, Centre for Medical Parasitology, University of Copenhagen, Copenhagen, Denmark, Department of Public Health, University of Copenhagen, Copenhagen, Denmark, Department of Infectious Diseases, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark, and Department of Clinical Microbiology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark, E-mail: lasse.vestergaard@dadlnet.dk. Marie Helleberg, Department of Infectious Diseases, Copenhagen University Hospital Rigshospitalet, University of Copenhagen, CHIP, Copenhagen, Denmark, E-mail: marie.helleberg@regionh.dk. Nyagonde Nyagonde, Tanzania National Institute for Medical Research, Tanga Center, Tanga, Tanzania, E-mail: drnyagonde@yahoo.com. Michala V. Rose, Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark, E-mail: michala.rose@gmail.com. Filbert Francis, National Institute for Medical Research, Tanga, Tanzania, E-mail: ffrancis8@gmail.com. Ola P. Theilgaard, Lægehuset i Hedehusene, Hedehusene, Denmark, E-mail: olaptheilgaard@gmail.com. Jens Asbjørn, Danish Health and Medicines Authority, Public Health Medical Officers of Southern Denmark, Kolding, Denmark, E-mail: asbjorn_1@hotmail.com. Ben Amos, InterACT Project, Muheza District Hospital, Muheza, Tanzania, E-mail: ben@teule.org.uk. Ib Christian Bygbjerg, Department of Public Health, University of Copenhagen, Copenhagen, Denmark, E-mail: iby@sund.ku.dk. Morten Ruhwald, Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark, E-mail: moru@ssi.dk. Pernille Ravn, Department of Pulmonary and Infectious Diseases, Nordsjaelland Hospital, Hillerød, Denmark, E-mail: peravn@gmail.dk.

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